TY - JOUR
T1 - PGC-1α and Reactive Oxygen Species Regulate Human Embryonic Stem Cell-Derived Cardiomyocyte Function
AU - Birket, Matthew J.
AU - Casini, Simona
AU - Kosmidis, Georgios
AU - Elliott, David A.
AU - Gerencser, Akos A.
AU - Baartscheer, Antonius
AU - Schumacher, Cees
AU - Mastroberardino, Pier G.
AU - Elefanty, Andrew G.
AU - Stanley, Ed G.
AU - Mummery, Christine L.
PY - 2013
Y1 - 2013
N2 - Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1α knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease
AB - Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1α knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease
U2 - https://doi.org/10.1016/j.stemcr.2013.11.008
DO - https://doi.org/10.1016/j.stemcr.2013.11.008
M3 - Article
C2 - 24371810
SN - 2213-6711
VL - 1
SP - 560
EP - 574
JO - Stem cell reports
JF - Stem cell reports
IS - 6
ER -